title: Prehospital hypertonic saline resuscitation attenuates the activation and promotes apoptosis of neutrophils in patients with severe traumatic brain injury.
abstract: BACKGROUND
  Activation of polymorphonuclear neutrophils (PMNs) is thought to contribute to traumatic brain injury (TBI). Since hypertonic fluids can inhibit PMN activation, we studied whether hypertonic fluid resuscitation can reduce excessive PMN activation in TBI patients.
  
  
  METHODS
  Trauma patients with severe TBI were resuscitated with 250 mL of either 7.5% hypertonic saline (HS; n = 22), HS + 6% dextran-70 (HSD; n = 22), or 0.9% normal saline (NS; n = 39), and blood samples were collected on hospital admission and 12 and 24 h after resuscitation. Polymorphonuclear neutrophil activation (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers and oxidative-burst activity, as well as spontaneous PMN apoptosis were measured by flow cytometry.
  
  
  RESULTS
  Relative to healthy controls, TBI patients showed increased PMN activation and decreased apoptosis of PMNs. In the HS group, but not in the HSD group, markers of PMN adhesion (CD11b, CD64) and degranulation (CD35, CD66b) were significantly lower than those in the NS group. These effects were particularly pronounced 12 h after resuscitation. Treatment with HS and HSD inhibited PMN oxidative burst responses compared with NS-treated patients. Hypertonic saline alone partially restored delayed PMN apoptosis. Despite these differences, the groups did not differ in clinical outcome parameters such as mortality and Extended Glasgow Outcome Scale.
  
  
  CONCLUSIONS
  This study demonstrates that prehospital resuscitation with HS can partially restore normal PMN activity and the apoptotic behavior of PMNs, whereas resuscitation with HSD was largely ineffective. Although the results are intriguing, additional research will be required to translate these effects of HS into treatment strategies that improve clinical outcome in TBI patients.
authors.affiliation: *Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria; †Defence Research and Development Canada, Toronto Research Centre and ‡Departments of Surgery and Critical Care Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; §Department of Surgery, Harborview Medical Center, University of Washington, Seattle, Washington; ∥Brain Injury Laboratory, Cara Phelan Centre for Trauma Research Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; and ¶American College of Surgeons, Department of Surgery, University of California, Irvine, California.
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Junger
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Rhind
authors.forename: Sandro B
authors.initials: SB
authors.lastname: Rizoli
authors.forename: Joseph
authors.initials: J
authors.lastname: Cuschieri
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
authors.forename: Pang N
authors.initials: PN
authors.lastname: Shek
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000097:blood; D015550:Cell Degranulation / Q000502:physiology; D003911:Dextrans / Q000627:therapeutic use; D004311:Double-Blind Method; D004632:Emergency Medical Services / Q000379:methods; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D010952:Plasma Substitutes / Q000627:therapeutic use; D016897:Respiratory Burst / Q000502:physiology; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003911:Dextrans; D010952:Plasma Substitutes; D012462:Saline Solution, Hypertonic